title: Elucidation of Rab27 recruitment by its effectors: structure of Rab27a bound to Exophilin4/Slp2-a.
abstract: Rab GTPases coordinate vesicular trafficking within eukaryotic cells by collaborating with a set of effector proteins. Rab27a regulates numerous exocytotic pathways, and its dysfunction causes the Griscelli syndrome human immunodeficiency. Exophilin4/Slp2-a localizes on phosphatidylserine-enriched plasma membrane, and its N-terminal Rab27-binding domain (RBD27) specifically recognizes Rab27 on the surfaces of melanosomes and secretory granules prior to docking and fusion. To characterize the selective binding of Rab27 to 11 various effectors, we have determined the 1.8 A resolution structure of Rab27a in complex with Exophilin4 RBD27. The effector packs against the switch and interswitch elements of Rab27a, and specific affinity toward Rab27a is modulated by a shift in the orientation of the effector structural motif (S/T)(G/L)xW(F/Y)(2). The observed structural complementation between the interacting surfaces of Rab27a and Exophilin4 sheds light on the disparities among the Rab27 effectors and outlines a general mechanism for their recruitment.
authors.affiliation: Structural Biology Research Center, Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), Tsukuba, Ibaraki 305-0801, Japan. leonard.chavas@manchester.ac.uk
authors.forename: Leonard M G
authors.initials: LM
authors.lastname: Chavas
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ihara
authors.forename: Masato
authors.initials: M
authors.lastname: Kawasaki
authors.forename: Seiji
authors.initials: S
authors.lastname: Torii
authors.forename: Tamami
authors.initials: T
authors.lastname: Uejima
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Kato
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Izumi
authors.forename: Soichi
authors.initials: S
authors.lastname: Wakatsuki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D025941:Protein Interaction Mapping; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D020691:rab GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D000075745:rab27 GTP-Binding Proteins
chemical_list: D008565:Membrane Proteins; C424134:Sytl2 protein, mouse; D000075745:rab27 GTP-Binding Proteins; C512962:Rab27a protein, mouse; D020691:rab GTP-Binding Proteins